Variant 5-122775115-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_003100.4(SNX2):c.12G>C(p.Glu4Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000267 in 1,590,122 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00030 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00026 ( 3 hom. )

Consequence

SNX2
NM_003100.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.63

Variant links:

Genes affected

SNX2 (HGNC:11173): (sorting nexin 2) This gene belongs to the sorting nexin family whose members contain the phosphoinositide-binding phox (PX) domain. The encoded protein is a component of the retromer complex which plays a role in protein sorting in the endocytic pathway. This protein may form oligomeric complexes with other family members. Alternate splicing results in multiple transcript variants of this gene. Pseudogenes associated with this gene are located on chromosomes 1 and 7. [provided by RefSeq, May 2013]

SNX2 links:

SNX2 (HGNC:):

SNX2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.018269092).

BS2

High AC in GnomAd4 at 45 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNX2	NM_003100.4 linkuse as main transcript	c.12G>C	p.Glu4Asp	missense_variant	1/15	ENST00000379516.7	NP_003091.2	O60749-1
SNX2	NM_001278199.1 linkuse as main transcript	c.-891G>C		5_prime_UTR_variant	1/15		NP_001265128.1	O60749-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNX2	ENST00000379516.7 linkuse as main transcript	c.12G>C	p.Glu4Asp	missense_variant	1/15	1	NM_003100.4	ENSP00000368831.2		O60749-1

Frequencies

GnomAD3 genomes

AF:

0.000296

AC:

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000916

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000250

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000466

AC:

AN:

210244

Hom.:

AF XY:

0.000479

AC XY:

AN XY:

112626

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000595

Gnomad ASJ exome

AF:

0.000332

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00175

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000294

Gnomad OTH exome

AF:

0.000956

GnomAD4 exome

AF:

0.000264

AC:

379

AN:

1437800

Hom.:

Cov.:

AF XY:

0.000312

AC XY:

222

AN XY:

712444

show subpopulations

Gnomad4 AFR exome

AF:

0.000180

Gnomad4 AMR exome

AF:

0.000938

Gnomad4 ASJ exome

AF:

0.000354

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00149

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000135

Gnomad4 OTH exome

AF:

0.000705

GnomAD4 genome

AF:

0.000295

AC:

AN:

152322

Hom.:

Cov.:

AF XY:

0.000322

AC XY:

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.000914

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000250

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000313

Hom.:

Bravo

AF:

0.000340

ExAC

AF:

0.000285

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 23, 2021

The c.12G>C (p.E4D) alteration is located in exon 1 (coding exon 1) of the SNX2 gene. This alteration results from a G to C substitution at nucleotide position 12, causing the glutamic acid (E) at amino acid position 4 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.097

T;.

Eigen

Benign

-0.17

Eigen_PC

Benign

-0.054

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.80

T;T

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.018

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.85

L;.

PrimateAI

Uncertain

0.69

PROVEAN

Benign

0.020

N;N

REVEL

Benign

0.089

Sift

Benign

0.25

T;T

Sift4G

Benign

0.83

T;T

Polyphen

0.58

P;.

Vest4

0.42

MutPred

0.54

Loss of glycosylation at P7 (P = 0.2497);Loss of glycosylation at P7 (P = 0.2497);

MVP

0.45

MPC

0.68

ClinPred

0.097

GERP RS

3.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.095

gMVP

0.15

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over